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GLENNIS LOGSDON, PH.D.

I'm a postdoctoral research fellow in Evan Eichler's laboratory at the University of Washington School of Medicine Department of Genome Sciences, where I study the sequence, variation, evolution, and function of human centromeres using computational, phylogenetic, and cell biological approaches

 

About Me

I am currently an NIH-funded postdoctoral research fellow at the University of Washington School of Medicine, where I study the sequence, structure, and evolution of human centromeric regions under the guidance of Dr. Evan Eichler

 

I previously obtained my Ph.D. in Biochemistry and Molecular Biophysics from the University of Pennsylvania Perelman School of Medicine in 2018, where I studied centromere establishment on human artificial chromosomes under the guidance of Dr. Ben Black.

 

I also obtained my B.A. in Biochemistry from the University of Pennsylvania in 2011, where I studied how noncoding RNAs generated from telomeres delay cellular senescence in budding yeast, under the guidance of Dr. Brad Johnson

 

As I transition to independence, I hope to apply my understanding of human centromere genetic and epigenetic variation to build new, more efficient centromeres on human artificial chromosomes.

Research Interests

Centromere sequence, structure, and evolution

I study a specialized region on each human chromosome: the centromere. The centromere is an essential locus that ensures the accurate inheritance of genetic information. At the sequence level, centromeres are comprised of near-identical repeats known as alpha-satellite, which are 171 bp long, organized in tandem, and can span multiple megabases on each chromosome. Because of the repetitive nature of these regions, centromeres have posed an enormous challenge to standard short-read sequencing and assembly methods, and consequently, all centromeres are absent from the human reference genome. During my postdoctoral training, I developed a sequence assembly method that combines two long-read sequencing data types (Oxford Nanopore Technologies ultra-long reads and Pacific Biosciences high-fidelity reads) to generate the first complete sequence of a centromere on a human autosome: chromosome 8. I also applied this method to resolve every remaining gap on chromosome 8, thereby generating the first telomere-to-telomere sequence of a human autosomal chromosome (Logsdon et al., Nature, 2021)

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The sequence, structure, epigenetic, and evolutionary map of the human chromosome 8 centromere. This centromere consists of a 2.08 megabasepair (Mbp) D8Z2 alpha-satellite higher-order repeat (HOR) array flanked by blocks of monomeric/divergent alpha-satellite. The D8Z2 HOR array is heavily methylated, except for a small, 73 kbp region that is hypomethylated. This hypomethylated region is centered within the 632 kbp centromeric chromatin domain, marked by the presence of the histone H3 variant, CENP-A. A pairwise sequence identity heat map reveals five major evolutionary layers and a mirror symmetry characteristic of active sequence homogenization in the core of the HOR array.

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The sequence, structure, and evolutionary map of the chromosome 8 centromere in chimpanzee, orangutan, and rhesus macaque. All three centromeres have a layered and symmetrical organization, similar to that observed in humans.

Analysis of the structure of the human chromosome 8 centromere revealed that it is comprised of five major evolutionary layers. To better understand the evolution of the chromosome 8 centromere, I generated complete sequence assemblies of the chromosome 8 centromere in chimpanzee, orangutan, and rhesus macaque and used these assemblies to reconstruct the evolutionary history of this centromere over the last 25 million years. I found that each centromere has the same layered and symmetrical organization observed in the human ortholog. Additionally, I confirmed that the alpha-satellite HOR structure evolved after apes diverged from Old World Monkeys less than 25 million years ago. Phylogenetic comparisons of the chromosome 8 centromeres revealed that it is evolving at least 2.2.-3.8 times faster than the rest of the human genome and is one of the most rapidly evolving regions identified. These findings support a model of centromere evolution where highly identical alpha-satellite repeats expand in the core of the centromere and push older, more divergent repeats to the edges in an assembly line fashion. 

Human artificial chromosomes with unique centromeres

Human artificial chromosomes (HACs) are engineered mini-chromosomes that acquire a functional centromere and are stably maintained in human cells. They have the potential to transform synthetic biology and permit the development of numerous radical developments in medicine because they can be used deliver genes or other DNA elements without integration into the host genome. Despite their utility, HACs are considered difficult to engineer because they typically require repetitive centromeric DNA sequences that can complicate cloning, handling, and their stability in bacterial propagation. Overcoming the barrier of repetitive centromeric DNA would accelerate HAC 

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Metaphase chromosome spreads containing a non-repetitive human artificial chromosomes (HAC; green). Non-repetitive HACs are able to form a functional centromere (marked by the histone H3 variant CENP-A; red) that ensures their stable propagation in cells for long periods of time. Scale bar = 10 microns.

development for their use in the clinic. During my Ph.D. training, I engineered a new type of HAC that is completely devoid of repetitive DNA. This HAC is comprised of DNA sequence from chromosome 4q21 and is stable in cells for several months. This new type of HAC surmounts barriers that have limited the progress of the construction of a synthetic human genome.

 

Featured publications

Logsdon GA, et al. The structure, function and evolution of a complete human chromosome 8. Nature.
2021 April 7. PDF

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Logsdon GA and Eichler EE. Mining the gaps of chromosome 8. Nature.
2021 May 14.. 
PDF

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Logsdon GA, Vollger MR, and Eichler EE. Long-read human genome sequencing and its applications.
Nat Rev Gen. 2020 June 5.. PDF

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Vollger MR*, Logsdon GA*, et al
Improved assembly and variant detection of a haploid human genome using single-molecule, high-fidelity long reads.. Ann Hum Genet. 2019 November 11. PDF
*Authors contributed equally to the work

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Logsdon GA, et al. Human artificial chromosomes that bypass centromeric DNA. Cell.
2019 July 25. PDF

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Logsdon GA, et al. Both tails and the centromere targeting domain of CENP-A are required for centromere establishment. J Cell Biol.
2015 March 2. PDF

Featured preprints

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Altemose N, Logsdon GA, et al. Complete genomic and epigenetic maps of human centromeres. bioRxiv. 2021 July 13. PDF

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Nurk S, . . . ,  Logsdon GA, et al. The complete sequence of a human genome. bioRxiv. 2021 May 27. PDF

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Giannuzzi G, Logsdon GA, et al. Alpha satellite insertions and the evolutionary landscape of centromeres. bioRxiv.
2021 May 6. PDF

 
 

Contact

Glennis Logsdon, Ph.D.

Department of Genome Sciences

University of Washington School of Medicine

 

Email: glogsdon [at] uw.edu

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